Scientists Map Chimpanzee Genome

Shows human DNA differs by just 3 percent, but that gap is already yielding scientific clues

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By E.J. MundellHealthDay Reporter

WEDNESDAY, Aug. 31, 2005 (HealthDay News) -- An international consortium of scientists announced Wednesday that they have completed a rough draft of the genome of the chimpanzee, the closest evolutionary relative to humans.

The genetic milestone offers the first comprehensive comparison of chimp DNA and human DNA, and key differences between the two are already providing clues to questions ranging from the pace of human genetic change, the origin of such diseases as Alzheimer's and Parkinson's, and even the continued existence of the human male.

"It's going to tell us important things about who we are and what we are -- medically, socially, and so forth. It's a pretty stunning achievement," said Dr. Robert Waterston, a member of The Chimpanzee Sequencing and Analysis Consortium and senior author of the study describing the genome, which is published in the Sept. 1 issue of Nature along with related research.

The completion of the genome of the chimpanzee -- Pan troglodytes -- marks just the fourth time any mammal's complete genetic code has been mapped and described in a major scientific publication (the other three milestones are the human, mouse and rat).

According to the Consortium, the DNA of a 24-year-old male chimpanzee named Clint, who died last year at the Yerkes National Primate Research Center in Atlanta, is 98.8 percent identical to that of the human genome.

That statistic is based on what geneticists call "single base pair" differences -- variance in the millions of arrangements of nucleotide molecules (labeled A, C, G, T) that make up individual genes.

The amount of base pair differences between chimps and humans is in line with expectations, "and account for quite a few differences in terms of numbers -- an estimated 35 million," explained consortium member Evan Eichler, a genetics researcher at the University of Washington in Seattle and lead author of a separate study in the journal.

But the real surprise came from something scientists haven't been able to measure up till now. Using new technology, they looked beyond these differences in tiny base pair changes to changes involving the duplication or deletion of genes themselves.

"If you think of the genome as the book of life, then the differences people have been looking at over the past 10 years have been typographical errors," Eichler explained. "But what we are looking at are redundancies in the text -- places where entire pages [genes] have been reprinted multiple times, or the page is missing."

These types of larger-scale changes, "only account for 5 million differences," Eichler said. "But in terms of the amount of genetic material that's different between the two species, they account for 2.7 percent, and that number is likely to be even greater -- up to 3.5 percent."

That wide a genetic gap between humans and chimps was somewhat unexpected, Eichler said. These differences -- emerging in the 6 million years since chimps and human parted evolutionary company -- may also yield important clues to distinctly human questions.

According to Waterston, who is chairman of the University of Washington's genome science department, human genetic change focused in one area -- gene transcription -- has been intriguingly rapid, and may explain why humans evolved relatively quickly compared to other mammals.

"Transcription factors are the genes that make proteins, that in turn regulate other genes," he explained. Because transcription occurs "upstream in the control hierarchy," mutations at this level would have a much more dramatic effect on human evolution than those further downstream, Waterston said.

This could explain "the large morphological changes that have happened in human evolution over a relatively short time -- 300,000 to 400,000 generations."

Then there's the chimp genome's implications for human medicine.

According to Eichler, chimp-human gene comparisons show that "humans have a lot more [gene] duplications than your average mammal."

That's important, he said, because "these duplications can cause rearrangements in regions of the genome that in turn can cause disease. There are about two dozen diseases right now that we know are caused by this duplication-mediated rearrangement."

Frans de Waal, director of the Living Links Center at Yerkes, agreed that future investigation of the primate and human genetic codes could yield medical gold.

"For example, there are certain diseases that chimpanzees don't have, such as Parkinson's and Alzheimer's -- everyone is, of course, very curious as to why humans have those, and what's responsible," said de Waal, who also authored an article for this week's issue of Science on the history of research into the chimpanzee.

A comparison of the human and chimp genome may even confirm the continued existence of half the human race: men.

Until now, researchers have puzzled over the fact that the male-only Y chromosome appeared to be shrinking over time.

"That's because every other chromosome has a pair," explained Jennifer Hughes, a post-doctoral researcher at the Whitehead Institute for Biomedical Research and lead author of a third study in Nature.

So, when mutations or deletions in a gene on the Y chromosome damage it beyond repair, that gene cannot be replaced and is essentially lost. Over hundreds of millions of years, that's meant that -- outside of a bunch of genes regulating sperm production -- the number of functional genes on the male Y chromosome has shrunk from 1,000 to just 16.

"This led to the 'The Y is Falling' hypothesis," Hughes said, with some experts estimating that Y carriers (i.e., men) would be rendered useless in about 10 million years.

But the chimp genome may have given potential fathers everywhere a reprieve.

Human males may have their sexual fidelity to thank for that, Hughes said.

Unlike humans, chimpanzee mating is by nature promiscuous, with every male in the troop attempting to fertilize any ovulating female. "So, unlike in humans, every chimp male's sperm has to fight really hard to fertilize a single egg," Hughes explained.

That may mean that, over time, genes on the Y chromosome that were dedicated to hardier sperm won out, with the less important non-sperm genes falling by the wayside because of naturally occurring mutations or deletions.

On the other hand, human males -- who are comparatively monogamous -- have retained those 16 Y genes, because their sperm-linked genes haven't played such a key role on the chromosome.

The bottom line? The Y chromosome -- and the human male -- appear to be "holding steady," Hughes said.

All the scientists agreed that insights like these are just the beginning.

According to Eichler, "the task now is to see which of these genetic regions that are changing rapidly have, in fact, genes that are important to what make chimps chimps -- and humans human."

To accompany the release of the genome and accompanying research in Nature, scientists from around the world published a flurry of related studies and commentaries Wednesday in the journal Genome Research as well as in a special early-release edition of Science.